[5] Human xenotransplantation offers a potential treatment for end-stage organ failure, a significant health problem in parts of the industrialized world.
[13][12] The first transplant of a non-genetically modified[14][15] pig's heart, lungs and kidneys into a human was performed in Sonapur, Assam, in India in mid-December 1996, and was announced in January 1997.
[14][16] The Indian cardiothoracic surgeon Dhani Ram Baruah and two of his associates, Jonathan Ho Kei-shing (of the Hong Kong-based Prince of Wales Medical Institute)[17] and C.S.
The kidney came from an animal with a knocked-out gene for the production of alpha gal sugars, which has been implicated in immune response to mammalian tissue.
The team has reported that the kidney has maintained optimal functioning for over a month, as evidenced by routine testing of creatinine and weekly biopsies.
In January 2022, doctors led by cardiothoracic surgeon Bartley P. Griffith and Muhammad M. Mohiuddin[34] at the University of Maryland Medical Center and University of Maryland School of Medicine performed a heart transplant from a genetically modified pig to a terminally ill patient, David Bennett Sr., who was ineligible for a standard human heart transplant.
The pig had undergone specific gene editing to remove enzymes responsible for producing sugar antigens that lead to hyperacute organ rejection in humans.
[36] In June and July 2022, surgeons at NYU Langone Health performed two genetically modified pig heart transplants into recently deceased humans.
[40] Certain procedures, some of which are being investigated in early clinical trials, aim to use cells or tissues from other species to treat life-threatening and debilitating illnesses such as cancer, diabetes, liver failure and Parkinson's disease.
[citation needed] The animal organ, probably from a pig or baboon could be genetically altered with human genes to trick a patient's immune system into accepting it as a part of its own body.
[45] It is used to predict the sensitivity of the transplanted tumor to various cancer treatments; several companies offer this service, including the Jackson Laboratory.
Chimpanzees were originally considered the best option since their organs are of similar size, and they have good blood type compatibility with humans, which makes them potential candidates for xenotransfusions.
Problems include their smaller body size, the infrequency of blood group O (the universal donor), their long gestation period, and their typically small number of offspring.
[49] They are inexpensive and easy to maintain in pathogen-free facilities, and current gene editing tools are adapted to pigs to combat rejection and potential zoonoses.
[35][23][27][31][39] To date,[citation needed] no xenotransplantation trials have been entirely successful due to the many obstacles arising from the response of the recipient's immune system.
It is mediated by the binding of XNAs (xenoreactive natural antibodies) to the donor endothelium, causing activation of the human complement system, which results in endothelial damage, inflammation, thrombosis and necrosis of the transplant.
Complement activation causes a cascade of events leading to: destruction of endothelial cells, platelet degranulation, inflammation, coagulation, fibrin deposition, and hemorrhage.
The binding of these antibodies activates the complement system, leading to a cascade of events that cause widespread clotting and inflammation in the transplanted organ's blood vessels.
The sudden loss of kidney function can result in the accumulation of waste products and fluids in the body, causing symptoms such as swelling, electrolyte imbalances, and potential life-threatening complications.
Acute vascular rejection requires de novo protein synthesis and is driven by interactions between the graft endothelial cells and host antibodies, macrophages, and platelets.
[55] Fibrosis in the xenograft occurs as a result of immune reactions, cytokines (which stimulate fibroblasts), or healing (following cellular necrosis in acute rejection).
Studies have also shown that some porcine transplant cells are able to induce human tissue factor expression, thus stimulating platelet and monocyte aggregation around the xenotransplanted organ, causing severe clotting.
[64] Xenotransplantation may increase the chance of disease transmission for 3 reasons: (1) implantation breaches the physical barrier that normally helps to prevent disease transmission, (2) the recipient of the transplant will be severely immunosuppressed, and (3) human complement regulators (CD46, CD55, and CD59) expressed in transgenic pigs have been shown to serve as virus receptors, and may also help to protect viruses from attack by the complement system.
Porcine herpesviruses and rotaviruses can be eliminated from the donor pool by screening, however others (such as parvovirus and circovirus) may contaminate food and footwear then re-infect the herd.
Because of this risk, the FDA has suggested any recipients of xenotransplants shall be closely monitored for the remainder of their life, and quarantined if they show signs of xenosis.
These antigens (foreign objects) are often treated with powerful immunosuppressive drugs that could, in turn, make the patient vulnerable to other infections and actually aid the disease.
[citation needed] In 2005, the Australian National Health and Medical Research Council (NHMRC) declared an eighteen-year moratorium on all animal-to-human transplantation, concluding that the risks of transmission of animal viruses to patients and the wider community had not been resolved.
[87] The four principles emphasize informed consent, the Hippocratic Oath to do no harm, using skills to help others, and protecting the right to quality care.
[89] United Kingdom guidelines state that patients have to agree to "the periodic provision of bodily samples that would then be archived for epidemiological purposes", "post-mortem analysis in case of death, the storage of samples post-mortem, and the disclosure of this agreement to their family", "refrain from donating blood, tissue or organs", "the use of barrier contraception when engaging in sexual intercourse", "keep both name and current address on register and to notify the relevant health authorities when moving abroad" and "divulge confidential information, including one's status as a xenotransplantation recipient to researchers, all health care professionals from whom one seeks professional services, and close contacts such as current and future sexual partners.
[89] The Food and Drug Administration (FDA) has also stated that if a transplantation takes place, the recipient must undergo monitoring for the rest of their lifetime and waive their right to withdraw.